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Propofol alters the mRNA profile in the developing mouse hippocampus

ABSTRACT: Propofol has been found to be toxic to developing neurons. The goal of the current study was to nominate novel genes predicted to underly the neurotoxicity, and use these candidates for future functional pathway assessment

ORGANISM(S): Mus musculus

PROVIDER: GSE106799 | GEO | 2017/11/14

SECONDARY ACCESSION(S): PRJNA418091

REPOSITORIES: GEO

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Propofol alters the mRNA profile in the developing mouse hippocampus

Project description:Propofol alters the mRNA profile in the developing mouse hippocampus

| PRJNA418091 | ENA

Effects of Propofol Treatment in Neural Progenitors Derived from Human Induced Pluripotent Stem Cells

Project description:Propofol is an intravenous anesthetic that has been widely used in the clinical setting. Besides its anesthetic effects, propofol has been reported to influence the regulation of autonomic system. Controversies exist with regards to whether propofol exposure is safe for pregnant women and young children. The recent emergence of human induced pluripotent stem cells (hiPSCs) has provided a promising and theoretically inexhaustible source of neural progenitor cells (NPCs) for drug testing, which could be extended to in vitro experiments for anesthetics such as propofol. NPCs derived from three hiPSC lines, NES-GFP (a NESTIN-GFP reporter), USCK7 (iPSCs derived from urine derived cells), and ND2-0 (NIH), were treated with propofol at different concentrations (20, 50, 100 and 300 µM) for 6 h or 24 h. Early and late cell injury, cell proliferation and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for propofol-treated and untreated control iPSC-NPCs. Propofol treatment of NPCs for 6 h at the clinically relevant concentration (20 or 50 µM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 µM) decreased NPC viability and induced apoptosis. Prolonged treatment of propofol for 24 h significantly decreased cell viability. In addition, 20 µM propofol treatment for 6 h did not alter global gene expression. Higher concentration of propofol exerted potential cytotoxicity via multiple cellular mechanisms. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration of propofol treatment could decrease NPC viability and induce apoptosis.

2017-07-21 | GSE101724 | GEO

Disturbance of key cellular subproteomes upon propofol treatment is associated with increased permeability of the blood-brain barrier

Project description:Background: Propofol is a short-acting anesthetic, which is often used for induction and maintenance of general anesthesia, sedation for mechanically ventilated adults and procedural sedation. Several side effects of propofol are known and a substantial number of patients suffer from post-operative delirium after propofol application. In this study, we analyzed the effect of propofol on the function and protein expression profile on a proteome-wide scale. Methods: We cultured human brain microvascular endothelial cells in the absence and presence of propofol and analyzed the permeability of the blood-brain barrier (BBB) by fluorescein passage and protein expression on a proteome-wide scale by mass spectrometry. Results: Propofol interfered with the function of the blood-brain barrier. This was not due to de-creased adhesion of propofol-treated human brain microvascular endothelial cells. The proteomic analysis revealed that some key pathways in these cells were disturbed, such as oxygen metabolism, DNA damage recognition and response to stress. Conclusions: Propofol has strong effects on protein expression which could explain several side effects of propofol.

2022-10-13 | PXD033856 | Pride

Enhanced hippocampal neurogenesis mediated by PGC-1α-activated OXPHOS after neonatal low-dose Propofol exposure

Project description:The regulation of gene expression after low-dose Propofol exposured in neural stem / progenitor cells (NSPCs)

2022-08-17 | GSE200968 | GEO

Enhanced hippocampal neurogenesis mediated by PGC-1α-activated OXPHOS after neonatal subclinical dose of Propofol exposure revealed by single-nuclei transcriptomic profiling

Project description:The change of cell lineage and regulation of gene expression after low-dose Propofol exposured in hippocampal of PND10 mice

2022-08-17 | GSE186216 | GEO

Gene expression of brain regions activated by sevoflurane and propofol

Project description:The basic mechanisms of action for general anesthesia are not fully understood. We thought differences in the neural activation sites of different types of anesthetics and differences in gene expression changes in those brain regions may lead to differences in the incidence of side effects. We performed gene expression analysis using microarrays in the identified regions that have been related to the mechanisms of anesthetic action and side effects. Gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics.

2021-12-22 | GSE192399 | GEO

Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems.

Project description:UnlabelledIron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2(hipp/hipp) mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2(hipp/hipp) mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2(hipp/hipp) mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems.Electronic supplementary materialThe online version of this article (doi:10.1007/s11689-010-9049-0) contains supplementary material, which is available to authorized users.

| S-EPMC2930796 | biostudies-literature

Gene expression of brain regions activated by sevoflurane and propofol

Project description:Gene expression of brain regions activated by sevoflurane and propofol

| PRJNA791342 | ENA

UPLC-MS-Based Serum Metabolic Profiling Reveals Potential Biomarkers for Predicting Propofol Responsiveness in Females

Project description:Although previous studies have shown that certain factors interfere with the sensitivity of propofol, the mechanisms for interindividual variability in response to propofol remain unclear. This study aimed to screen the metabolites to predict patients' sensitivity to propofol and to identify metabolic pathways to explore possible mechanisms associated with propofol resistance. Sera from 40 female patients undergoing elective hysteroscopic surgery in a prospective cohort propofol study were obtained before the administration of propofol. The patients' responsiveness to propofol was differentiated based on propofol effect-site concentration. Serum samples from two sets, a discovery set (n = 24) and an independent validation set (n = 16), were analyzed using ultraperformance liquid chromatography coupled with mass spectrometry based untargeted metabolomics. In the discovery set, 494 differential metabolites were screened out, and then 391 potential candidate biomarkers with the area under receiver operating characteristic curve >0.80 were selected. Pathway analysis showed that the pathway of glycerophospholipid metabolism was the most influential pathway. In the independent validation set, six potential biomarkers enabled the discrimination of poor responders from good and intermediate responders, which might be applied to predict propofol sensitivity.

2021-09-29 | MTBLS2311 | MetaboLights

Sevoflurane Exposure Alters Long Non-coding RNA and Messenger RNA Profiles in the Neonatal Mouse Hippocampus

Project description:The focus of current study is to investigate the effect of developing sevoflurane exposure on lncRNA profiles and molecular signaling involvement in neurotoxicity. An Expression Microarray assay (V3.0) and data analysis services were provided by Arraystar Inc. (Rockville, MD) to assess and compare the global abundance of 27,427 lncRNAs and 18,855 mRNAs in the hippocampi of mice exposed to either sevoflurane or normal air controls.

2021-02-17 | GSE155770 | GEO

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